Precursors of Proteases channels (Fig. 30.4 ) and causes an outflow of Cl− into the duct lumen. This secondarily drives the activity of an adjacent antiporter that exchanges the chloride ions for bicarbonate. CFTR is also permeable to bicarbonate. Thus the bicarbonate secretory process is dependent on CFTR, which provides an explanation for the defects in pancreatic function seen in the disease cystic fibrosis, in which CFTR is mutated. The bicarbonate needed for this secretory process is derived from two sources. Some is taken up across the basolateral membrane of the ductular epithelial cells via the sodium-bicarbonate cotransporter type 1 (NBC-1) symporter. Recall that the process of gastric acid secretion results in an increase in circulating bicarbonate ions, which can serve as a source of bicarbonate to be secreted by the pancreas. However, bicarbonate can also be generated intracellularly via the activity of the enzyme carbonic anhydrase. The net effect is to move HCO3 − into the lumen and thereby increase the pH and volume of pancreatic juice.
•Fig. 30.3 ParticipationofsecretinandHCO3−secretioninaclassicnegative-feedbackloopthatrespondstoafallinluminalpHintheduodenum.˜ pH in duodenum S cells Ductular bicarbonate secretion Secretin release ˜°°° •Fig. 30.4 Iontransportpathwaysinpancreaticductcells.CA,carbonicanhydrase;CFTR,cysticfibrosistransmembraneconductanceregulator;NBC-1,sodium/bicarbonatecotransporter(symporter)type1;NHE-1,sodium-hydrogenexchanger(antiporter)type1.NBC-1 NHE-1 Duct cell 2K˜Cl °HCO3 Duct lumen CFTR Na˜Na˜3Na˜2HCO3 H2CO3 CO2 ˜ H2O H2O ˜CO2 ˜H˜H2CO3 CA Cl °Na˜K˜H2O °2HCO3 °H˜˜ HCO3 °°HCO3°
Characteristics and Control of Acinar Secretion
In contrast to the pancreatic ductules, where secretin is the most important physiological agonist, CCK plays the predominant role at the level of the acinar cells. Thus it is important to understand how release of CCK is controlled during the small intestinal phase of the response to a meal.